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XB-ART-37945
PLoS One June 18, 2008; 3 (6): e2471.
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Binding of sFRP-3 to EGF in the extra-cellular space affects proliferation, differentiation and morphogenetic events regulated by the two molecules.

Scardigli R , Gargioli C , Tosoni D , Borello U , Sampaolesi M , Sciorati C , Cannata S , Clementi E , Brunelli S , Cossu G .


Abstract
BACKGROUND: sFRP-3 is a soluble antagonist of Wnts, widely expressed in developing embryos. The Wnt gene family comprises cysteine-rich secreted ligands that regulate cell proliferation, differentiation, organogenesis and oncogenesis of different organisms ranging from worms to mammals. In the canonical signal transduction pathway Wnt proteins bind to the extracellular domain of Frizzled receptors and consequently recruit Dishevelled (Dsh) to the cell membrane. In addition to Wnt membrane receptors belonging to the Frizzled family, several other molecules have been described which share homology in the CRD domain and lack the putative trans-membrane domain, such as sFRP molecules (soluble Frizzled Related Protein). Among them, sFRP-3 was originally isolated from bovine articular cartilage and also as a component of the Spemann organizer. sFRP-3 blocks Wnt-8 induced axis duplication in Xenopus embryos and binds to the surface of cells expressing a membrane-anchored form of Wnt-1. Injection of sFRP-3 mRNA blocks expression of XMyoD mRNA and leads to embryos with enlarged heads and shortened trunks. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that sFRP-3 specifically blocks EGF-induced fibroblast proliferation and foci formation. Over-expression of sFRP-3 reverts EGF-mediated inhibition of hair follicle development in the mouse ectoderm while its ablation in Xenopus maintains EGF-mediated inhibition of ectoderm differentiation. Conversely, over-expression of EGF reverts the inhibition of somitic myogenesis and axis truncation in Xenopus and mouse embryos caused by sFRP-3. In vitro experiments demonstrated a direct binding of EGF to sFRP-3 both on heparin and on the surface of CHO cells where the molecule had been membrane anchored. CONCLUSIONS/SIGNIFICANCE: sFRP-3 and EGF reciprocally inhibit their effects on cell proliferation, differentiation and morphogenesis and indeed are expressed in contiguous domains of the embryo, suggesting that in addition to their canonical ligands (Wnt and EGF receptor, respectively) these molecules bind to each other and regulate their activities during embryogenesis.

PubMed ID: 18560570
PMC ID: PMC2424011
Article link: PLoS One


Species referenced: Xenopus
Genes referenced: actb actl6a dvl2 egf egfr fgf8 frzb hacd4 hsp90ab1 inhba myod1 myoz3 pdgfa prss1 wnt1
Antibodies: Somite Ab1


Article Images: [+] show captions
References [+] :
Assimacopoulos, Identification of a Pax6-dependent epidermal growth factor family signaling source at the lateral edge of the embryonic cerebral cortex. 2003, Pubmed